Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons

Ipsaro, Jonathan J, O'Brien, Paul A, Bhattacharya, Shibani, Palmer, Arthur G, Joshua-Tor, Leemor (March 2021) Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons. Cell Reports, 34 (13). p. 108914. ISSN 2211-1247

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Abstract

The Piwi-interacting RNA (piRNA) pathway safeguards genomic integrity by silencing transposable elements (transposons) in the germline. While Piwi is the central piRNA factor, others including Asterix/Gtsf1 have also been demonstrated to be critical for effective silencing. Here, using enhanced crosslinking and immunoprecipitation (eCLIP) with a custom informatic pipeline, we show that Asterix/Gtsf1 specifically binds tRNAs in cellular contexts. We determined the structure of mouse Gtsf1 by NMR spectroscopy and identified the RNA-binding interface on the protein's first zinc finger, which was corroborated by biochemical analysis as well as cryo-EM structures of Gtsf1 in complex with co-purifying tRNA. Consistent with the known dependence of long terminal repeat (LTR) retrotransposons on tRNA primers, we demonstrate that LTR retrotransposons are, in fact, preferentially de-repressed in Asterix mutants. Together, these findings link Asterix/Gtsf1, tRNAs, and LTR retrotransposon silencing and suggest that Asterix exploits tRNA dependence to identify transposon transcripts and promote piRNA silencing.

Item Type:	Paper
Subjects:	bioinformatics Investigative techniques and equipment > microscopy > Cryo-electron microscopy bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification organism description > animal > insect > Drosophila bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organism description > animal bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene silencing organism description > animal > insect bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > recombination bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA expression > transposable elements bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > zinc finger proteins
CSHL Authors:	Ipsaro, Jonathan J. Joshua-Tor, Leemor
Communities:	CSHL labs > Joshua-Tor lab CSHL Cancer Center Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program CSHL Cancer Center Shared Resources > Mass Spectrometry Service CSHL Cancer Center Shared Resources > Next Generation Sequencing Service CSHL Cancer Center Shared Resources > Sequencing Technology & Analysis Service
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	30 March 2021
Date Deposited:	28 Apr 2021 19:47
Last Modified:	13 Feb 2024 17:04
PMCID:	PMC8283736
URI:	https://repository.cshl.edu/id/eprint/39949

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